The role of PKCε-dependent signaling for cardiac differentiation

Protein kinase Cepsilon (PKCe) exerts a wellknown
cardio-protective activity in ischemia–reperfusion
injury and plays a pivotal role in stem cell proliferation and
differentiation. Although many studies have been performed
on physiological and morphological effects of
PKCe mis-expression in cardiomyocytes, molecular information
on the role of PKCe on early cardiac gene expression
are still lacking. We addressed the molecular role of
PKCe in cardiac cells using mouse cardiomyocytes and rat
bone marrow mesenchymal stem cells. We show that PKCe
is modulated in cardiac differentiation producing an
opposite regulation of the cardiac genes NK2 transcription
factor related, locus 5 (nkx2.5) and GATA binding protein
4 (gata4) both in vivo and in vitro. Phospho-extracellular
regulated mitogen-activated protein kinase 1/2 (p-ERK1/2)
levels increase in PKCe over-expressing cells, while pkce
siRNAs produce a decrease in p-ERK1/2. Indeed, pharmacological
inhibition of ERK1/2 rescues the expression
levels of both nkx2.5 and gata4, suggesting that a reinforced
(mitogen-activated protein kinase) MAPK signaling
is at the basis of the observed inhibition of cardiac gene
expression in the PKCe over-expressing hearts. We demonstrate
that PKCe is critical for cardiac cell early gene
expression evidencing that this protein is a regulator that
has to be fine tuned in precursor cardiac cells.